This project forms the basis of a Clinical Associate Physician grant for Linda Anne DiMeglio, MD. It will be used as a supplement for the General Clinical Research Center (GCRC) at the Indiana University School of Medicine. The broad objective is to provide a five-year period of mentored support for Dr. DiMeglio to facilitate her development as an independent clinical investigator. The application includes both a systematic career development plan and a clinical research project. The career development plan includes: l) completion of the Indiana University GCRC Department of Medicine two year Clinical Investigator Training Enhancement Program, 2) completion of a Master's Degree Ln Public Health, and 3) careful mentorship by Munro Peacock, MD, Ora Pescovitz, MD, and other researcher physicians to foster Dr. DiMeglio's evolution into a productive and independent clinical research investigator. The clinical research proposal describes a study to evaluate the efficacy and safety of "Bisphosphonate Therapy for Osteogenesis Imperfecta (OI)." OI is a heritable disorder of collagen synthesis. Affected persons have low bone mineral density and experience multiple fractures and progressive bony deformity. In its most severe form, the disorder is lethal in infancy. To date, no effective therapy exists for this debilitating condition. Improyements in bone mineral density and in fracture rates in a small number of children treated with intravenous bisphosphonates have been reported. The efficacy of oral bisphosphonates has not been established. We will characterize the changes effected by oral bisphosphonate therapy and compare them to a regimen of intravenous bisphosphonate therapy in a group of children with OI.